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Chronic tuberculosis (TB) disease, which requires months-long chemotherapy with multiple antibiotics, is defined by diverse pathological manifestations and bacterial phenotypes. Targeting drug-tolerant bacteria in the host is critical to achieving a faster and durable cure for TB. In order to facilitate this field of research, we need to consider the physiology of persistent MTB during infection, which is often associated with the nonreplicating (NR) state. However, the traditional approach to quantifying bacterial burden through colony enumeration alone only informs on the abundance of live bacilli at the time of sampling, and provides an incomplete picture of the replicative state of the pathogen and the extent to which bacterial replication is balanced by ongoing cell death. Modern approaches to profiling bacterial replication status provide a better understanding of inter- and intra-population dynamics under different culture conditions and in distinct host microenvironments. While some methods use molecular markers of DNA replication and cell division, other approaches take advantage of advances in the field of microfluidics and live-cell microscopy. Considerable effort has been made over the past few decades to develop preclinical in vivo models of TB infection and some are recognized for more closely recapitulating clinical disease pathology than others. Unique lesion compartments presenting different environmental conditions produce significant heterogeneity between Mycobacterium tuberculosis populations within the host. While cellular lesion compartments appear to be more permissive of ongoing bacterial replication, caseous foci are associated with the maintenance of M. tuberculosis in a state of static equilibrium. The accurate identification of nonreplicators and where they hide within the host have significant implications for the way novel chemotherapeutic agents and regimens are designed for persistent infections. [ABSTRACT FROM AUTHOR]

Outdoor decorative fountains usually attract residents to visit. However, opportunistic pathogens (OPs) can proliferate and grow in the stagnant fountain water, posing potential health risks to visitors due to the inhalation of spaying aerosols. In this study, the abundance of selected OPs and associated microbial communities in three large outdoor decorative fountain waters were investigated using quantitative PCR and 16S rRNA sequencing. The results indicated that Mycobacteria avium and Pseudomonas aeruginosa were consistently detected in all decorative fountain waters throughout the year. Redundancy analysis showed that OPs abundance was negatively correlated with water temperature but positively correlated with nutrient concentrations. The gene copy numbers of M. avium varied between 2.4 and 3.9 log 10 (gene copies/mL), which were significantly lower than P. aeruginosa by several orders of magnitude, reaching 6.5-7.1 log 10 (gene copies/mL) during winter. The analysis of taxonomic composition and prediction of functional potential also revealed pathogenic microorganisms and infectious disease metabolic pathways associated with microbial communities in different decorative fountain waters. This study provided a deeper understanding of the pathogenic conditions of the outdoor decorative fountain water, and future works should focus on accurately assessing the health risks posed by OPs in aerosols., Competing Interests: The authors declare there is no conflict., (© 2024 The Authors This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits copying, adaptation and redistribution, provided the original work is properly cited (http://creativecommons.org/licenses/by/4.0/).)

Mycobacteria are a unique group of microorganisms. They are characterised by exceptional adaptability and durability. They are capable of colonisation and survival even in very unfavourable conditions. In addition to the well-known obligate human pathogens, Mycobacterium tuberculosis and M. leprae, more than 200 other species have been described. Most of them form a natural part of the microflora of the external environment and thrive in aquatic and soil environments especially. For many of the mycobacterial species associated with human disease, their natural source has not yet been identified. From an ecological point of view, mycobacteria are saprophytes, and their application in human and animal diseases is opportunistic. Most cases of human disease from saprophytic mycobacteria occur in immunocompromised individuals. This adaptability and resilience to environmental pressures makes treatment of mycobacterial diseases (most often sapronoses and less often zoonoses) and permanent eradication of mycobacteria from the environment very difficult. Saprophytic mycobacterial diseases (sapronoses) are chronic and recurrent due to the fact of repeated endogenous or exogenous re-exposure. Therefore, knowledge regarding their occurrence in soil and dust would aid in the prevention of saprophytic mycobacterioses. In conjunction, their presence and ecological significance in the environment can be revealed. [ABSTRACT FROM AUTHOR]